Bismuth oxide salicylate

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 January 2010 to 1 February 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with EU and OECD guidelines and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

yes

Remarks:

See below

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

yes

Remarks:

See below

Principles of method if other than guideline:

Deviations from the Guideline: Deionised water was used for the determination of the solubility in water of Bismuth sub¬salicylate, instead of doubly distilled water, as validation showed, that usage of deionised water was acceptable for the determination of the solubility in water of Bismuth compounds. Additionally, commercially available doubly distilled water may have a TOC of up to 5 ppm.

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Water solubility:

>= 0.19 - <= 22.83 mg/L

Temp.:

20 °C

Remarks on result:

other: Standard deviation of all samples was 8.9 mg/L

Details on results:

Most replicates showed poor correspondence. Standard deviation of all samples (flask method) was 8.90 mg/L, corresponding to a relative standard deviation of 96.7 %. The concentration of Bismuth subsalicylate in water lay in the range of 0.19 - 22.83 mg/L. During equilibration, the concentration of Bi in flask 1 had been well reproducible. Therefore, flasks 2-6 were sampled on day 4 and measured, but the values showed large variations. The repetition of sampling and measurement on day 7 gave as large variations, and only moderate correspondence to the measurements on day 4. Dependency of solubility on pH was not observed.
In comparison standard deviation of all samples (column elution method) was 0.954 mg/L, corresponding to a relative standard deviation of 4.2 %. Therefore the mean at the plateau was 22.97 ± 0.954 mg/L.
Accuracy measurements via standard addition showed a correlation of 0.997, indicating that no matrix effects were present.
A defined value for the water solubility of Bismuth subsalicylate cannot be stated. The test item doesn't show reproducible dissolution in deionised water (flask method), although the influence of oxygen was minimised by working under inert gas (Argon).
No observations arousing doubts concerning the accuracy of the results and the validity of the study were made.

Measurements during Equilibration Flask Method

The data which was acquired during equilibration is presented in the following table:

Day	Flask	Temperature in °C	pH	Dilution factor	Bi Concentration (diluted sample) in mg/L	Difference to previous sample %	Concentration test item in mg/L
1	1	20.0	6	10.1	1.133	-	19.83
2	1	20.0	5	10.1	1.304	15.1	22.83
3	1	20.0	6	10.1	1.062	-18.6	18.59
4	1	20.0	6	10.1	0.999	-5.9	17.48

pH was measured using pH paper.

The concentrations of the test item were calculated from the measured Bi concentrations and the content of Bi in the test item (57.715%).

After the analysis of the sample of day 4, the plateau was considered as reached.

Measurements at Plateau Flask Method

The following table gives the values which were measured at the plateau:

Flask	2	3	4	5	6
pH	4.036	4.040	4.410	4.708	4.236
First Measurement (day 4)
Concentration Bi in mg/L (diluted sample)	0.904	0.477	0.011 (< LOQ)	0.033 (< LOQ)	1.189
Dilution factor	10.1	10.1	10.1	10.1	10.1
Concentration Bi in mg/L (original sample)	9.13	4.81	0.11	0.33	12.01
Concentration test item in mg/L	15.82	8.34	0.19	0.58	20.81
Second Measurement (day 7)
Concentration Bi in mg/L (diluted sample) repetition	0.400	0.168	0.055	0.045	0.058
Dilution factor	10.1	10.1	10.1	10.1	10.1
Concentration Bi in mg/L (original sample) repetition	4.04	1.70	0.56	0.46	0.59
Concentration test item in mg/L (repetition)	7.00	2.95	0.96	0.79	1.02

Because of high deviation of flasks 2 - 6 from flask 1, measurements of flasks 2 - 6 on day 7 was repeated and showed incomparable values. Results Flask Method

The measurements of the days 1 - 7 (Flask 1) were included in the calculation of the mean and presented in the following table:

Day	Flask	Mean Conc. (mg/L)	Total Mean (mg/L)	Total Stand. Dev.
1	1	19.83	9.20	8.90 (96.7 %)
2	1	22.83
3	1	18.59
4	1	17.48
4	2	15.82
4	3	8.34
4	4	0.19
4	5	0.58
4	6	20.81
7	2	7.00
7	3	2.95
7	4	0.96
7	5	0.79
7	6	1.02

The concentration of Bismuth subsalicylate in water lay in the range of 0.19 and 22.83 mg/L.

Measurements of the Test Item Column Elution Method

The analytical determinations were made using the collected aqueous fractions. The change in volume was taken into account when calculating the concentration in the original samples.

The analytical determinations which were performed are presented in the following tables: Measurements at flow rate 24.88 ml/h:

Sample #	Concentration Bi mg/L	Dilution factor	Factor	Concentration Bismuth subsalicylate mg/L	pH
1	1.148	10.162	0.57715	20.22	6
2	1.330	10.190	0.57715	23.48	6
3	1.343	10.174	0.57715	23.67	6
4	1.323	10.186	0.57715	23.36	6
5	1.310	10.165	0.57715	23.07	6
6	1.334	10.193	0.57715	23.57	6

Measurements at flow rate 12.26 ml/h:

Sample #	Concentration Bi mg/L	Dilution factor	Factor	Concentration Bis­muth subsalicylate mg/L	pH
7	1.330	10.208	0.57715	23.517	6
8	1.333	10.200	0.57715	23.551	6
9	1.300	10.203	0.57715	22.988	6
10	1.283	10.203	0.57715	22.684	6
11	1.267	10.182	0.57715	22.355	6
12	1.312	10.208	0.57715	23.205	6

At each flow rate, the plateau was considered as reached after the analysis of five consecutive samples (differences below 30% and no upward tendency).

Results Column Elution Method

The measurements of both flow rates were included in the calculation of the mean since the differences between the measured concentrations lay below 30%.

Flow Rate	Mean Concentration (mg/L)	Standard Deviation	Total Mean (mg/L)	Total Standard Deviation.
24.88	22.89	1.328	22.97	0.954 (4.2 %)
12.26	23.05	0.472

Mean at the plateau is 22.97 ± 0.954 mg/L

Conclusions:

Interpretation of results (migrated information): slightly soluble (0.1-100 mg/L)
Using the flask method, the concentration of Bismuth subsalicylate in water (all samples) lay in the range of 0.19 - 22.83 mg/L at 20 ± 0.5 °C with a mean at the plateau 9.20 ±8.90 mg/L at 20 ± 0.5 °C (mean value ± standard deviation of six individual vessels).

Executive summary:

After two pre-tests (pre-test according guideline and column elution method), the water solubility of bismuth subsalicylate was estimated to be > 10 mg/L. Therefore, the flask method was employed. For the flask method, different amounts of the test item were weighed into each of six individual vessels, water was added to achieve concentrations ranging from 800 - 1200 mg/L, and the vessels were shaken at 19.1 - 21.7 °C.

On the days 1, 2, 3 and 4, vessel 1 was taken from the shaking apparatus and stored at 20 ± 0.5 °C for equilibration. Samples were withdrawn, filtrated and analysed using AAS as shaking of the test vessels was continued.

No differences above 15% in the concentration of the solution could be determined between the sampling dates 3 and 4, supporting the hypothesis, that the maximum concentration of the test item had been reached. Therefore, on day 4, vessels 2-6 were sampled and analysed in the same fashion. Because of high deviation of flasks 2-6 from flask 1, measurements of flasks 2 - 6 on day 7 was repeated and showed incomparable values.

Using the flask method, the concentration of Bismuth subsalicylate in water (all samples) lay in the range of 0.19 - 22.83 mg/L at 20 ± 0.5 °C with a mean at the plateau 9.20 ±8.90 mg/L at 20 ± 0.5 °C (mean value ± standard deviation of six individual vessels).

In comparison, the concentration of Bismuth subsalicylate in water (all samples) with the column elution method had reached: 22.97 ± 0.954 mg/L at 21.2 ± 0.4 °C.

Description of key information

The water solubility of bismuth subsalicylate ranges from 0.19 to 22.83 mg/L (mean = 9.2 mg/L) at 20 ± 0.5 °C.

Key value for chemical safety assessment

Water solubility:

9.2 mg/L

at the temperature of:

20 °C

Additional information

A study was conducted to determine the water solubility of bismuth subsalicylate in accordance with OECD Guideline 105 and EU Method A.6.

Using the flask method, the concentration of bismuth subsalicylate in water (all samples) lay in the range of 0.19 - 22.83 mg/L at 20 ± 0.5 °C with a mean at the plateau 9.20 ±8.90 mg/L at 20 ± 0.5 °C (mean value ± standard deviation of six individual vessels).